Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA260312 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The diversity of human breast cancer subtypes has led to the hypothesis that breast cancer is a number of different diseases arising from cells at various stages of differentiation. We have derived clonal multipotent metastatic mammary cancer stem cells from the polyomavirus middle T mouse model of breast cancer, that can differentiate into luminal, myoepithelial and alveolar cells. When injected orthotopically at low-density, the resulting tumors express estrogen and progesterone receptors. With continued passage in vivo, the tumor cells undergo additional epigenetic and/or genetic changes that result in upregulation of Her2 expression or clonal expansion of cells that give rise to basal-like or claudin-low tumors. As in human tumors, the more aggressive tumor subtypes express nuclear p53. The temporal sequence of events suggests that contrary to current dogma, multiple tumor subtypes can originate from a single multipotent cancer stem cell that undergoes evolution during tumor progression. Furthermore, these data raise the possibility that a human polyomavirus may be a causative agent in spontaneous forms of human breast cancer. Three spontaneous PyVmT tumors and forty cell line derived tumors were analyzed. To generate cell line derived tumors, 10^6 tumor cells were injected orthotopically into four abdominal mammary fat pads in syngeneic C57Bl/6 female mice. After 6-8 weeks the mice were euthanized and the tumors excised and frozen at -80°C. One tumor per mouse 8-10mm in diameter was used for array analysis. RNA was extracted using the RNeasy kit (Qiagen) with on column DNA removal.
2014-09-12 | E-GEOD-61138 | biostudies-arrayexpress
Project description:The diversity of human breast cancer subtypes has led to the hypothesis that breast cancer is a number of different diseases arising from cells at various stages of differentiation. We have derived clonal multipotent metastatic mammary cancer stem cells from the polyomavirus middle T mouse model of breast cancer, that can differentiate into luminal, myoepithelial and alveolar cells. When injected orthotopically at low-density, the resulting tumors express estrogen and progesterone receptors. With continued passage in vivo, the tumor cells undergo additional epigenetic and/or genetic changes that result in upregulation of Her2 expression or clonal expansion of cells that give rise to basal-like or claudin-low tumors. As in human tumors, the more aggressive tumor subtypes express nuclear p53. The temporal sequence of events suggests that contrary to current dogma, multiple tumor subtypes can originate from a single multipotent cancer stem cell that undergoes evolution during tumor progression. Furthermore, these data raise the possibility that a human polyomavirus may be a causative agent in spontaneous forms of human breast cancer.
2014-09-12 | GSE61138 | GEO
Project description:Mammary epithelium is hierarchically organized, with multipotent basal mammary stem cells (MaSCs) producing both luminal and basal cells during development or upon transplantation. Recent studies suggested that most breast cancers, including Basal-Like breast cancer (BLBC), might originate from luminal cells, and oncogenic events, such as ectopic expression of PIK3CA(H1047R), could induce multipotency in committed luminal cells. p53 is the most commonly mutated gene in human breast cancer; in particular, its inactivating mutations are found in most BLBCs, raising a question as to whether p53-loss plays a key role in acquisition of multipotent MaSC-like properties by luminal cells. By in situ lineage-tracing, we found that induced loss of p53 in Keratin 8 (K8)+ luminal cells led to their clonal expansion, due to increased cell cycle activity and attenuated apoptosis control, but did not directly affect their luminal identity. All induced mice eventually developed either Claudin-Low mammary tumors with 9qA1 (Yap1) amplification or Basal-Like tumors with 6qA1-A2 (Met) amplification. These data suggest that although p53 does not directly control the luminal fate, its loss facilitates acquisition of MaSC-like properties by luminal cells and predisposes them to development of mammary tumors with loss of luminal identity.
2016-12-20 | GSE77497 | GEO
Project description:Mammary epithelium is hierarchically organized, with multipotent basal mammary stem cells (MaSCs) producing both luminal and basal cells during development or upon transplantation. Recent studies suggested that most breast cancers might originate from luminal cells, and oncogenic events, such as ectopic expression of PIK3CAH1047R, could induce multipotency in committed luminal cells. p53 is the most commonly mutated gene in human breast cancer; in particular, its inactivating mutations are found in most triple-negative breast cancers, raising a question as to whether p53-loss plays a key role in acquisition of MaSC-like properties by luminal cells. By in situ lineage tracing, we found that induced loss of p53 in Keratin 8 (K8)+ luminal cells led to their clonal expansion, in part due to increased proliferation, but did not directly affect their luminal identity. Expansion of luminal cells, in particular oestrogen receptor-positive luminal cells, was observed 3-4 weeks after induced p53-loss, which was accompanied by increased expression of cell cycle genes and downregulation of genes related to immune microenvironment, p53 downstream pathway and apoptosis control. All induced mice eventually developed mammary tumours with 9qA1 (Yap1) amplification and/or 6qA2 (Met) amplification. The resulting tumours exhibited a MaSC-like expression signature and most closely resembled Claudin-Low breast cancer. Overall, these data suggest that although p53 does not directly control the luminal fate, its loss facilitates acquisition of MaSC-like properties by luminal cells and predisposes them to development of mammary tumours with loss of luminal identity. Our data also suggest that Claudin-Low breast cancer can originate from luminal cells, possibly upon transition through a basal-like state.
2016-12-20 | GSE77496 | GEO
Project description:Somatic DNMT3A R882 codon mutations drive the most common form of clonal haematopoiesis (CH) and are associated with increased acute myeloid leukaemia (AML) risk1,2. Preventing expansion of DNMT3A-R882-mutant haematopoietic stem/progenitor cells (HSPCs) may therefore avert progression to AML. To identify DNMT3A-R882-mutant-specific vulnerabilities, we conducted a genome-wide CRISPR screen on primary mouse Dnmt3aR882H/+ HSPCs. Amongst the 640 vulnerability genes identified, many were involved in mitochondrial metabolism and metabolic flux analysis confirmed enhanced oxidative phosphorylation usage in Dnmt3aR882H/+ vs Dnmt3a+/+ (WT) HSPCs. We selected citrate/malate transporter Slc25a1 and complex I component Ndufb11, for which pharmacological inhibitors are available, for downstream studies. In vivo administration of SLC25A1 inhibitor CTPI2 and complex I inhibitors IACS-010759 and metformin, suppressed post-transplantation clonal expansion of Dnmt3aR882H/+, but not WT, LT-HSCs. The effect of metformin was recapitulated using a primary human DNMT3A-R882 CH sample. Notably, analysis of 412,234 UK Biobank participants revealed that individuals taking metformin had markedly lower prevalence of DNMT3A-R882-mutant CH, after controlling for potential confounders including glycated haemoglobin, diabetes and body mass index. Collectively, our data propose that modulation of mitochondrial metabolism as a therapeutic strategy for prevention of DNMT3A-R882-mutant AML.
2025-02-06 | MTBLS12201 | MetaboLights
Project description:The retinoblastoma tumor suppressor, Rb, is implicated in luminal-B and basal-like breast carcinomas, yet its effect on mammary gland development and causal role in breast cancer subtypes remain undefined. Here we show that conditional deletion of Rb in mouse mammary epithelium led to expansion of the stem/progenitor cells and to focal acinar hyperplasia with squamous metaplasia. These uniform lesions progressed into histologically diverse, transplantable mammary adenocarcinomas and adenosquamous carcinomas with features of luminal-B or basal-like carcinomas. A subset of basal-like but none of the luminal-B tumors expressed mutant p53. These results demonstrate a causative role for Rb in the etiology of breast cancer subtypes and implicate p53 status as a determinant of tumor phenotype after Rb loss. Keywords: reference x sample Will be updated soon
2010-07-06 | E-GEOD-14457 | biostudies-arrayexpress
Project description:Feline mammary carcinoma (FMC) is the most prevalent reproductive tumor in queens, characterized by aggressive metastatic and short survival times. Protein phosphorylation plays a crucial role in cell regulation, with dysregulation linked to cancer progression, including human breast cancer.
2026-03-05 | PXD061475 | JPOST Repository
Project description:Gene signature of adult mammary stem cells and mammary cancer stem cells (Affymetrix)
| PRJNA174682 | ENA
Project description:Gene signature of adult mammary stem cells and mammary cancer stem cells (RT_PCR)
| PRJNA174744 | ENA
Project description:This study investigates the immune characteristics of tissue-resident memory T cells in the human fallopian tube in high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing (scRNA-seq) and paired T-cell receptor sequencing (scTCR-seq) were performed on samples from non-cancerous fallopian tube tissue, metastatic omental tumors, and peripheral blood from HGSOC patients. The dataset enables analysis of tissue-resident T cell populations, clonal relationships across tissues, and immune features associated with tumor progression. These data provide a resource for studying tissue-resident T cell heterogeneity, clonal expansion, and tumor-associated immune responses in ovarian cancer.
2026-04-03 | GSE301378 | GEO